Antibacterial activity of N-benzenesulfonyl derivatives against Staphylococcus aureus

MARTINEZ SR; MIANA G; ALBESA I; MAZZIERI MR; BECERRA MC

Córdoba

Otro; 3° Reunión Internacional de Ciencias Farmacéuticas. RICiFa; 2014

Dpto. Farmacia. Fac. Ciencias Químicas-UNC y la Univ. Nac. de Rosario.

Antibacterial activity of N-benzenesulfonyl derivates against Staphylococcus aureus Keywords: Staphylococcus aureus, reactive oxygen species, N-benzenesulfonyl derivatives. The indiscriminate clinical use of many very efficient antibiotics has led to an unfortunate emergence of bacteria able to resist them. The call for greater effort to develop new classes of antibiotics is fully justified. A lead discovery project, a library of N-benzenesulfonyl derivatives of bioactive heterocyclic compounds was design and prepared. The approach was based on the combination of two groups that are known to be active, benzenesulfonyl (BS) and 1, 2, 3, 4-tetrahydroquinoline heterocycle (THQ). The objective of this study was to evaluate the antibacterial activity of BS-THQ and to investigate the production of reactive oxygen species. Minimum inhibitory concentration (MIC) of BS-THQ was determined in Staphylococcus aureus ATCC 29213 and a methicillin-resistant S.aureus ATCC (MRSA) 43300 by using the standard tube dilution method according to Clinical Laboratory Standard Institute (CLSI). The reactive oxygen species were evaluated by Nitro Tetrazolium Blue (NBT) assay and by Fluorescent Microscopy (FM). Transmission electronic Microscopy (TEM) provides useful insight into the mechanism of action of antibacterial agent. The MIC of BS-THQ was200 µg/mL for both isolates tested. The generation of ROS in S.aureus ATCC 29213 was particularly higher than the MRSA, showing 15.6 and 2.8% of ROS, respectively, at sub-MIC concentrations of BS-THQ. Similar results were obtained by the qualitative method FM. BS-THQ (sub-MIC concentrations) affects the morphology of S.aureus ATCC 29213. Clear disorganization of the cytoplasmic membrane was revealed by TEM. Hydrophobic properties of BS-THQ could explain the interaction with the bacterial membrane. This interaction would facilitate the generation of ROS, altering the bacterial physiology and the oxidative stress balance. As a result, the disruption of the membrane and the generation of reactive oxygen species are suggested as factors that compromise the viability of S. aureus strains exposed to BS-THQ.